Ultra-thin photo-polymer coatings and uses thereof

ABSTRACT

The invention provides methods for forming ultra-thin hydrophilic polymeric coatings on articles, as well as articles formed therefrom. The coatings are formed by irradiating a composition including a polymer having pendent photoreactive groups while the composition is in contact with a surface of the article.

CROSS-REFERENCE TO RELATED APPLICATION

The present non-provisional Application is a divisional of U.S. patentapplication Ser. No. 11/594,501, filed on Nov. 08, 2006, whichapplication claims priority under 35 U.S.C. 119(e) from commonly ownedprovisional U.S. Patent Application having Ser. No. 60/734,961, filed onNov. 8, 2005, both of which are fully incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates to methods for forming extremely thinhydrophilic photo-polymeric coatings, micro-structured ornano-structured articles having these coatings, and methods relating tothe use of articles having these ultra-thin coatings.

BACKGROUND OF THE INVENTION

Materials that are used to fabricate articles that contact fluids, suchas filters, biosensors, and implantable medical devices, are generallychosen for their bulk physical properties rather than for the propertiesthese materials may confer to the article surface. As a result, whilethe object may have desirable properties such as strength andelasticity, its surface may not be optimized for interactions withfluids. Conventional methods and materials for the surface modificationof such devices can be used, for instance, to decrease proteinadsorption, increase wettability and lubricity, and decrease thrombusformation and bacterial colonization.

Conventional coating processes typically involve steps of preparing acoating composition that includes polymeric material, applying thecompositions to the surface of a substrate, and then drying and curingthe composition to form a polymeric coating on the surface of thesubstrate. In many coating procedures, coating compositions are appliedto the surface by dip-coating or by spraying, and then are allowed todry. However, these conventional coating techniques and reagents arefrequently not well designed for applications that require very thincoatings. More typically these techniques result in coatings that aregreater than 0.5 microns in thickness.

Various attempts have been made to provide passivated,biomolecule-compatible synthetic surfaces. These attempts have includedthe design and production of improved plastics, as well as the use ofthin-film coatings of plastic, silica, semiconductor, and metalsurfaces. Thin film coatings have tended to rely upon the adsorption andthermochemical bonding of preformed hydrophilic and surfactant polymers,in situ polymerization/crosslinking to form hydrophilic but insolublepolymeric films, or photochemical bonding of preformed hydrophilic andsurfactant polymers after an article has been dip-coated in a coatingsolution.

Relatively thinner coatings can be prepared by vapor depositionpolymerization (VDP). In VDP, monomer product is vaporized in a reactionchamber in the presence of a substrate. The vaporized monomer radicalresublimates on the surface of the substrate, and reacts with othermonomer radicals on the surface to form a thin polymer layer. Parylene™(poly(para-xylylene)) coatings are commonly formed by VDP processes.Although these coatings are relatively very thin, they typically do nothave thicknesses of less than 100 nm. Typically, poly(para-xylylene)coated layers are in the range of about 0.1 micron to about 75 micronsin thickness. Even these relatively thin coatings that are formed byplasma deposition processes have the potential to provide coatings thatmay be too thick for some applications.

More recently, the preparation of “ultra-thin” coatings has beenachieved. As referred to herein, “ultra thin” coatings can be consideredto have a thickness of about 20 nm or less. Such ultra-thin coatings canbe particularly useful for applications wherein a substantially thickercoating would otherwise obscure at least a part of the function of thedevice. These applications for “ultra thin” coatings are numerous andinclude, for example, coating surfaces that provide either small poresizes or structural features of less than about one micron in size.

One general approach to providing an ultra-thin coating has beendescribed in U.S. Pat. No. 6,689,473 (Guire et. al.) which describesforming an ultra-thin coating on a surface using amphiphilic-selfassembling monolayer (SAM) molecules and latent reactive groups (such asphotoreactive groups). The SAM molecules can be covalently coupled to asurface and/or coupled together to form a thin-coated layer on thesurface of the article. These SAM-coated surfaces are useful for anumber or purposes, including passivation against protein absorption andbacterial adherence, passivation against non-specific absorption on abiosensor, and preparation of an oligonucleotide array. Self-assembledmonolayer (“SAM”) technology has been used to generate monomolecularfilms of biological and non-biological (e.g., synthetic polymeric)molecules on a variety of substrates. The formation of such monolayersystems is versatile and can provide a method for the in vitrodevelopment of bio-surfaces which are able to mimic naturally occurringmolecular recognition processes. SAMs also permit reliable control overthe packing density and the environment of an immobilized recognitioncenter or multiple centers, at a substrate surface.

Despite some progress, advancement in this technological area is stillneeded to provide ultra-thin coatings having properties such as completeand uniform surface coverage, hydrophilic properties, minimalnonspecific attraction for biomolecules and cells, sufficient stabilityand durability, broad applicability to various material surfaces, andease and reproducibility for forming the coating. Furthermore, thecoating should be easily formed by conventional manufacturing processes.In some cases it would also be desirable to prepare coatings that areresistant to conventional sterilization techniques that are used toprepare medical articles for use. In addition, it is also desirable toutilize coating materials that are not costly or that are relativelystraightforward to synthesize.

What is clearly needed are methods and reagents for providing improvedsurface coatings, including those having further improved combinationsof the various desirable properties listed above.

SUMMARY OF THE INVENTION

The present invention relates to forming ultra-thin hydrophilicphoto-polymeric coatings on target surfaces. The ultra-thin polymericcoatings are useful in many applications, and can be formed to change orimprove the properties of the target surface, or to provide a coatedlayer that is useful for the immobilization of other agents, forexample, biological agents, such as proteins, nucleic acids, or cells.

Generally, according to the invention, the ultra-thin coatings areformed by preparing a coating solution that includes a hydrophilicphoto-polymer (i.e., a hydrophilic polymer having pendent photoreactivegroups) contacting the substrate with the coating solution, and thenirradiating the substrate to promote formation of an ultra-thinpolymeric layer on the surface of the substrate. The coating process isperformed without drying down the coating solution on the surface of thesubstrate prior to the step of irradiating.

According to the methods of the present invention, it has beendemonstrated that the ultra-thin photo-polymer layer formed on thesurface can be less than 5 nm in thickness. However, thicker coatingsusing methods of the present invention can also be obtained, forexample, by altering the coating parameters. In many of these cases, theresultant coatings can still be considered to be “ultra-thin” (less than20 nm in thickness).

Despite the coatings being extremely thin, the coatings still providedesirable properties that are consistent with properties of thepolymeric material of the coating. For example, an ultra-thin layer ofhydrophilic polymer formed according to the invention shows excellentwettability characteristics.

The ultra-thin coatings described herein can be very useful whenprovided to the surface of articles having micro-structured ornano-structured features. In these cases, the overall function of thearticle in a particular application may necessitate that the coating isproportional to the features on the article. For example, an ultra-thinhydrophilic polymeric coating can be formed on a material having verysmall pores (e.g., a filter), such as less than 5 μm, and even less than0.25 μM in size (250 nm) described herein. Because the photo-polymericcoating formed is so thin relative to the pore size, the pore size isnot significantly reduced by formation of the coating, and therefore theperformance of the substrate is not compromised. Other devices that thehydrophilic photo-polymers of the present invention can be applied toinclude, but are not limited to, molecular electronics, such assemiconductors fabricated from silicon materials, silver surfaces havingorganic molecules, chemically stable semiconductor layers,cluster/molecule/semiconductor assemblies, cluster networks,micro-electro-mechanical-systems (MEMS), actuators, micro- andnano-scale integrated systems, micro-fluidic bio-chips, micro-flowsystems, and nano-electronic devices for DNA characterization.

In some aspects of the invention, the ultra-thin coating is formed onthe surface of a textured or structured article, such as one selectedfrom the group of articles having fibers, pores, filaments, threads,processes, apertures, or combinations thereof. One advantage of usingthe method of the invention is that the photo-polymer layer can beformed at one or more very specific and small locations on the surfaceof the device. That is, when the photo-polymer composition is in contactwith the surface of the device, defined activating light irradiation canbe applied to one or more very specific locations on the surface toprovide an ultra thin coating at the specific location(s). In somecases, the irradiation pattern may correspond to the micro- ornano-structured surface of the device.

Surprisingly, it has also been found that even though the coatingsdescribed are extremely thin, they also have good durability. That is,the coating can be physically challenged and retain its hydrophilicproperties following the challenge. This demonstrates that the coatingthat is formed, even though extremely thin, is very strong.

Another distinct advantage of the ultra-thin hydrophilic coatings of theinvention relates to its ability to be rapidly and sufficientlyhydrated. Thicker coatings may take a long time to wet, and thus take along time to provide a hydrophilic surface, due to a greater amount ofwater that must be drawn into the coating. The ultra-thin coatings,however, are rapidly saturable.

This can be an advantage in forming a coating on a porous substrate.When exposed to a polar or aqueous liquid, a filter having an ultra-thincoating as described herein can rapidly be wetted and pass the liquidthrough the filter. The flux of the liquid is not hindered, and thefilter is not subject to excessive pressure, which may be caused by anegative pressure (vacuum) or a forward pressure.

Another advantage of the present invention relates to methods forforming the ultra-thin coated layer, as in many aspects the coating canbe rapidly and efficiently prepared. As demonstrated herein, a coatingcan be formed on the substrate by contacting the substrate with acoating solution (for example, by immersion) and irradiating thesubstrate in contact with the coating solution to form the coated layer.Steps that involve drying the coating composition are not required. Thisis in comparison to other coating processes that can require additionalsteps to prepare the coating. Furthermore, the supplemental addition ofreagents, such as reagents that may be required to promote the formationof a polymeric coating, are not required. In turn, the inventive methodsdescribed herein are of economic advantage since there is a savings withregard to the time and reagents used in the coating process.

In some aspects of the invention, the substrate that is coated has ahydrophobic surface and also is a poor source of, or provides noabstractable hydrogens. In these aspects, it is thought that inpreparing the ultra-thin coatings the photoreactive group of thephoto-polymer promotes association with the substrate surface and thenirradiation of the photoreactive groups promotes bonding between thephotoreactive groups and portions of the polymer, which is a bettersource of abstractable hydrogen atoms as compared to the substratesurface. In this case, covalent bonds are predominantly formed betweenthe photoreactive groups and the polymers of the coating composition toform an ultra-thin crosslinked network of hydrophilic polymers on thesurface of the article.

Therefore, in some aspects, the invention provides an article having ahydrophilic polymeric coating having a thickness of 20 nm or less, thecoating comprising a plurality of hydrophilic polymers covalently bondedvia pendent photo-reactive groups.

In some aspects, the invention provides a method for forming ahydrophilic coating on a surface of an article, the coating having athickness of less than 20 nm. The method includes the steps of (a)contacting all or a portion of the article with a coating compositioncomprising a hydrophilic polymer comprising at least one pendent latentphotoreactive group; and while the coating composition is in contactwith the substrate, (b) irradiating the composition to activate thephotoreactive groups to form the hydrophilic polymeric coating having athickness of 20 nm or less.

In other aspects of the invention, a water soluble crosslinking agentthat includes two or more pendent photoreactive groups is used to formthe ultra thin coating. The crosslinking agent can be added to improveproperties of the coating, such as durability. In forming the coating,the crosslinking agent can provide additional bonding between thehydrophilic polymers of the ultra-thin coated layer. For example,methods that utilize a crosslinking agent can include the steps of (a)contacting all or a portion of the article with a coating compositionthat includes (i) a hydrophilic polymer having pendent photoreactivegroups and (ii) a water soluble crosslinking agent having pendentphotoreactive groups; and while the coating composition is in contactwith the surface of the article, and (b) irradiating the surface of thearticle.

In some aspects, the article has a surface that is hydrophobic and apoor source of abstractable hydrogens and is formed of ahalogen-containing polymeric material, such as an article that isfabricated from a chloro- or fluoro-polymer. Exemplary polymericmaterials include chloro- or floro-saturated polymers, such as PTFE.

In other aspects of the invention the ultra-thin hydrophilic coating isprovided to an article having a porous structure. The article having aporous structure is preferably formed from hydrophobic material, and canoptionally include material that provides sources of abstractablehydrogens.

Exemplary articles having porous surfaces include filters with smallpore sizes. While the inventive hydrophilic coatings described hereincan be useful for articles having any pore size, they are particularlyuseful for filters having pore sizes of about 5 microns or less, forexample, having pore sizes ranging between about 0.05 microns and about5 microns. The methods described herein can be performed to provide ahydrophilic coating to the surface of the filter wherein the coatingdoes not compromise the performance of the filter. In some aspects theinvention provides a filter comprising a hydrophilic photo-polymericcoating having a thickness of 20 nm or less and having an average poresize of 5 μm or less.

In a related aspect, the invention therefore also provides methods forthe preparation of a filter having a hydrophilic coating, wherein thefilter has a small pore sizes and wherein the hydrophilic coating doesnot significantly hinder the flux of fluid through the pores.

Also, according to some aspects of the invention, it has also beendiscovered that the use of hydrophilic polymers having a molecularweight of less than about 500 kDa can improve the formation andqualities of the ultra-thin coated layer. In some aspects hydrophilicpolymers are used having a molecular weight in the range of about 10 kDato about 500 kDa. Therefore, in another aspect, the invention provides amethod for forming an ultra thin hydrophilic coating comprising thesteps of (a) providing a coating composition that includes a hydrophilicpolymer having pendent photoreactive groups, wherein the hydrophilicpolymer has a molecular weight of 500 kDa or less, (b) contacting all ora portion of the article with the coating composition, and (c)irradiating the surface of the article while the coating composition isin contact with the surface of the article. The invention alsocontemplates articles having an ultra-thin coating of less than 20 nmformed from a hydrophilic polymer having a molecular weight of 500 kDaor less, or in some aspects in the range of 10 kDa to 500 kDa.

The hydrophilic polymer used to form the ultra thin coating includes twoor more pendent photoreactive groups, and generally includes a pluralityof pendent photoreactive groups. In some aspects, the hydrophilicpolymer includes a plurality of photoreactive groups that are randomlyspaced along the polymer backbone. Such polymers can be formed by thecopolymerization of hydrophilic monomers and monomers having pendentphotoreactive groups.

DETAILED DESCRIPTION

The embodiments of the present invention described herein are notintended to be exhaustive or to limit the invention to the precise formsdisclosed in the following detailed description. Rather, the embodimentsare chosen and described so that others skilled in the art canappreciate and understand the principles and practices of the presentinvention.

All publications and patents mentioned herein are hereby incorporated byreference. The publications and patents disclosed herein are providedsolely for their disclosure. Nothing herein is to be construed as anadmission that the inventors are not entitled to antedate anypublication and/or patent, including any publication and/or patent citedherein.

As used herein, the term “layer” or “coated layer” refers to a layer ofone or more coated materials of sufficient dimensions (for example,thickness and area) for its intended use over the entire, or less thanthe entire, portion of an article surface. A “coating” as describedherein can include one or more “coated layers,” each coated layerincluding one or more coating components. In some aspects of theinvention the coating consists of a single coated layer ofphoto-polymeric material.

The present invention is directed to methods for preparing coatings onsurfaces of articles wherein it is desired to have an extremely thinhydrophilic polymeric layer, articles having extremely thin hydrophilicpolymeric coatings, and also various methods for using these coatedarticles.

Since the ultra-thin coatings are particularly useful in a wide varietyof applications, the invention is not limited to particular uses.Rather, the teachings of the invention demonstrate how thephoto-polymeric coatings can be formed on a number of different articlesthat can be used in a variety of different applications. Based on thisdisclosure and the knowledge in the art, one would be able to formultra-thin coating on a desired substrate to impart, for example,hydrophilic properties to the surface of the substrate.

In particular, the ultra-thin coatings of the invention are useful whenit is desired to form a rapidly wettable, ultra-thin coating on thesurface of an object. Therefore, the ultra-thin coatings can be used inareas of technology wherein the coated object is intended to come intocontact with a polar fluid, such as water. Other exemplary fluidsinclude buffers, beverages, and biological fluids.

In some aspects, the coatings of the present invention are used in areasof technology relating to the movement of fluids, such as water,including, but not limited to, fluid conduits, fluid filtration,microfluidics, biosensors, medical devices, etc. However, upon review ofthe disclosure, it will be apparent that the ultra-thin hydrophilicphoto-polymer coatings of the present invention can be used in manydifferent technological areas.

In some aspects of the invention, the ultra-thin coating is formed onthe surface of a textured or structured article. Exemplary textured orstructured article include those having fibers, pores, filaments,threads, processes, apertures, or combinations thereof. The ultra-thincoatings have been found to be particularly useful for coating articleshaving structural features ranging from nanometers to micrometers insize.

The ultra-thin hydrophilic photo-polymer layer can be formed on thesurface of a device that includes any suitable substrate material. Thematerials from which a substrate or device is fabricated are referred toherein as “substrate material(s)” or “device material(s).” In someaspects the layer can be formed on devices or articles constructed fromsubstantially all metal materials, such as alloys. The ultra-thin layercan also be formed on devices constructed from both non-metal and metalmaterials, for example, substrates having at least a portion of thesurface including a metal. A metal surface can also be formed as a thinsurface layer on a device formed from a non-metal material. Suchsurfaces can be formed by any method including sputter coating metalonto all or portions of the surface of the device.

Metals that can be used as substrate materials include platinum, gold,or tungsten, as well as other metals such as rhenium, palladium,rhodium, ruthenium, titanium, nickel, and alloys of these metals, suchas stainless steel, titanium/nickel, nitinol alloys, andplatinum/iridium alloys. These metals, including other alloys orcombinations, can be suitable substrates to be used in a method ofcoating with the hydrophilic photo-polymers as described herein.

The surface of metal articles can optionally be treated to alter thesurface chemistry. In many embodiments of the invention where it isdesired to provide an ultra-thin hydrophilic photo-polymeric coating toa surface, it is preferred that if the surface chemistry is altered, itis done in such as manner as not to significantly add to the thicknessof the material that will be applied to the surface (including thephoto-polymer layer). For example, some metal or glass surfaces can betreated with a silane reagent, such as a hydroxy- or chloro-silane.

Other surfaces that can optionally be provided with an ultra-thincoating include those that comprise human tissue such as bone,cartilage, skin and teeth; or other organic materials such as wood,cellulose, compressed carbon, and rubber. Other contemplated materialsinclude ceramics such as, but not limited to, silicon nitride, siliconcarbide, zirconia, and alumina, as well as glass, silica, and sapphire.Combinations of ceramics and metals can also be coated.

The ultra-thin polymeric layer can be formed on the surface of plasticarticles. “Plastic” is used in its broadest sense and includes allplastic substrates, including thermosets and thermoplastics. The plasticarticles that are contemplated as substrates can range from veryflexible plastic articles to very rigid plastic articles. In someaspects of the invention the ultra-thin hydrophilic photo-polymercoating is formed on a substrate that is somewhat rigid, or moderatelyrigid.

In some embodiments of the invention, the ultra-thin hydrophilicphoto-polymeric coating is formed on the surface of a plastic substrate,wherein the plastic substrate includes a polymeric material thatprovides a poor source of, or no source of abstractable hydrogens. Inthese embodiments very little covalent coupling, or no covalentcoupling, occurs between the hydrophilic photo-polymer and the surfaceof the device.

Surprisingly, it has been discovered that an ultra-thin coating havingsignificant durability can be formed on these types of plastic surfaces.In these embodiments, it is speculated that the ultra-thin coating isformed by covalent coupling between hydrophilic photo-polymers via thephotoreactive groups, thereby forming an extremely thin crosslinkednetwork of photopolymers on the surface of the device. This type oflayer formation can also be referred to as “inter-photo-polymercoupling”.

As used herein, the term “durability” refers to the wear resistance of apolymer coating, or the ability of a coating to be maintained on adevice surface when subjected to forces typically encountered during use(for example, normal force, shear force, and the like). A more durablecoating is less easily removed from a substrate by abrasion. Durabilityof a coating can be assessed by subjecting the device to conditions thatsimulate use conditions. The ultra-thin coatings can be formed on thedevice surface in such a manner as to withstand the effect of shearforces that may be encountered in some aspects of the invention duringuse of the coated article. In these cases, such forces could otherwiseresult in delamination of the coating from the body member.

Another class of polymers that can be used as substrate materialsinclude halogenated polymers, for example, chlorinated and/orfluorinated polymers. In some embodiments the substrate materialincludes a perhalogenated polymer. “Perhalogenated” refers to polymerswherein any carbon-bonded hydrogen is replaced by a halogen atom such aschlorine or fluorine. In some embodiments the substrate materialincludes a “perfluorinated” polymer, referring to polymers wherein allof the carbon-bonded hydrogens are replaced with fluorine. In someembodiments “partially fluorinated” polymers are used, referring tosubstrate polymers wherein not all carbon-bonded hydrogens are replacedby fluorine atoms, for example, at least one-fourth of the hydrogenatoms bonded to carbon atoms are replaced with fluorine atoms. A“fluorinated thermoplastic” refers to a fluoropolymer having a distinctmelting point, as distinguished from amorphous materials such asfluoroelastomers that usually do not have such a melting point. A“thermoplastic elastomer” refers to a rubber-like material that can beprocess like thermoplastic materials.

Fluoroplastics can be useful as substrate materials because ofproperties they confer, such as chemical resistance properties. However,it is often difficult to covalently bond materials to the surface ofsubstrates constructed from fluoropolymers because fluoropolymer-basedsubstrates have surfaces that are poorly reactive or non-reactive. Thesefluoropolymers, including those commonly known under the trade name ofTeflon™, have very lubricious and hydrophobic surface properties.

Examples of perhalogenated polymers that can be used as substratematerials include perfluoroalkoxy (PFA) polymers, such as Teflon™ andNeoflon™; polychlorotrifluoroethylene (PCTFE); fluorinated ethylenepolymers (FEP), such as polymers of tetrafluoroethylene andhexafluoropropylene; poly(tetrafluoroethylene) (PTFE); and expandedpoly(tetrafluoroethylene) (ePTFE). These polymers typically have meltingtemperatures ranging from about 100° C. to about 330° C.

Examples of partially fluorinated polymers include various combinationsof interpolymerized units of TFE (tetrafluoroethylene),hexafluoropropylene (HFP), vinylidene fluoride (VDF), perfluoro alkyl oralkoxy vinyl ethers, and nonfluorinated olefins. Materials in this classinclude TFE/HFP/VDF copolymers such as THV (a polymer oftetrafluoroethylene, hexafluoropropylene and vinylidene fluoride), ETFE(a polymer of tetrafluoroethylene and ethylene), HTE (a polymer ofhexafluoropropylene, tetrafluoroethylene, and ethylene), polyvinylidenefluoride (PVDF; such as Kynar™, Foraflon™, Solef™, Trovidur™), TFE/P(tetrafluoroethylene/propylene), and ethylene chlorotrifluoroethylene(ECTFE) copolymers, such as Halar™.

Other fluoropolymers are known in the art and described in variousreferences, such as, W. Woebcken, Saechtling International PlasticsHandbook for the Technologist, Engineer and User, 3rd Ed., (HanserPublishers, 1995) pp. 234-240.

To illustrate the use of a fluoropolymer as a substrate materialaccording to the present invention and to demonstrate the advantagesthat the inventive coatings can provide to these types of substrates,the preparation of a hydrophilic coating of a photo-polymer on thesurface of an ePTFE substrate is described.

ePTFE can be manufactured into a variety of substrate articles ordevices useful in a wide variety of technologies. For example, ePTFEtubing is imparted with unique physical properties that make it idealfor use in medical devices, electronic insulators, high performancefilters, and a number of other applications.

One particularly useful application involves coating a porous substrate,such as a filter, with a hydrophilic photo-polymer to form an ultra-thinhydrophilic layer. A filter substrate is described as it exemplifies anideally suitable substrate for formation of an ultra-thin hydrophiliccoated layer using the photo-polymers as described herein. Filtershaving the inventive ultra-thin coating can be employed for a variety offiltering applications, including fluid filtering. The term “filter”refers to any device that can block, trap, and/or modify particles ormolecules passing through the device. A “fluid” refers to any form ofreadily flowing material, including liquids and gases. In some cases thefilter can be an “active” filter, meaning that the filter is capable ofaction upon one or more components, or “target species,” of a fluidstream, whether by catalysis, reaction, or some combination thereof, sothat a modified specie(s) is formed. For example, in an active filter, acatalytic species can be coupled to the ultra-thin hydrophilicphoto-polymeric layer.

In some aspects, in addition to pendent photoreactive groups, thehydrophilic polymer can also include pendent binding moieties. A“binding moiety” refers to any sort of chemical group that can bind orinteract with a target species, such as an analyte, that is present in asample (this may be more specifically referred to as a “target speciesbinding moiety”). The binding moiety can include naturally occurringmolecules or derivatives of naturally occurring molecules, or syntheticmolecules, such as small organic molecules, or a larger syntheticallyprepared molecules, such as polymers. Examples of binding moietiesinclude polypeptides, nucleic acids, polysaccharides, and portions ofthese types of molecules that can bind a target species. Hydrophilicpolymers having pendent photoreactive groups and pendent bindingmoieties have been described in, for example, U.S. Pat. No. 5,858,653,and U.S. Pat. No. 6,121,027.

The ultra-thin hydrophilic photo-polymeric layer can be formed on thesurface of an article having a “microporous substrate,” referring toarticles having pores on the order of about 0.05 μm to about 5 μm inwidth. Microporous substrates can include expanded microporous PTFEmembranes.

Examples of suitable microporous layers include, but are not limited to,microporous ePTFE membranes, other polymeric (organic or inorganic)membranes, multi-layer membranes, filled membranes, asymmetricmembranes, other non-woven or woven materials, and open cell foams.

Some conventional filters can be fabricated from felt and/or fabricmaterials, which can be prepared from a variety polymeric materials, andas described herein include fluoropolymers, aramids, and glasses.Selection of the type of materials used may be based on the liquid thatis being filtered, as well as the operating conditions of the system andthe type of particulates being filtered.

For example, PTFE membranes can be incorporated as surface laminates onconventional filter elements. Porous PTFE membranes can be prepared by anumber of different known processes, such as by expanding PTFE asdescribed in U.S. Pat. Nos. 4,187,390, 4,110,392 and 3,953,566, toobtain expanded, porous PTFE. Expanded PTFE (ePTFE) in the form of amembrane has a number of desirable properties that make it aparticularly desirable filtration material. For example, ePTFE typicallyhas many microscopic holes or “micropores”, such as on the order of 0.05μM to 10 μM across, which allow fluid molecules to pass through butrestrict the passage of particulates, such as fine dust and the like.Additionally, the surface of an expanded PTFE membrane can be readilycleaned of accumulated contaminants, vastly improving the operative lifeof the filter.

The ultra-thin hydrophilic polymeric coating of the present inventioncan be particularly useful in filter technologies when it is desired toprovide a hydrophilic surface on a filter that is fabricated from amaterial that is not hydrophilic. As discussed herein, the ultra-thincoatings can provide a number of advantages in this area, includingproviding a hydrophilic surface without significantly reducing poresize, providing a rapidly wettable hydrophilic surface, providing adurable coating, and forming a hydrophilic coating in a straightforwardand efficient manner.

A filter having an ultra-thin hydrophilic photo-polymeric coating canalso find use in a number of different technological areas. For example,these filters can be used in the electronics industry wherein there is aneed for ultrapure, particle-free chemicals, such as solvents, acids,bases, ultrapure water, and photoresists. High purity reagents are veryimportant in the production of DRAMs and many other criticalmicroelectronic devices. Electronics grade chemicals and ultrapure waterused in semiconductor manufacture are often filtered by microfilters tosubmicron levels, for removal of yield-damaging particulates. Thecoatings of the present invention can be used in conjunction withfilters to provide these reagents of high purity.

In other embodiments of the invention, the ultra-thin hydrophilicphoto-polymeric coating is formed on the surface of a plastic substrate,wherein the plastic substrate includes a polymeric material thatprovides a good source of abstractable hydrogens. That is, the polymericmaterial of the substrate can provide a surface to which thephoto-polymer can react with, when activated. In these embodiments, thesubstrate includes one or more polymers that provide hydrogen atoms thatare readily abstracted by an activated photoreactive group of theinvention. For these substrates, the hydrophilic photo-polymer canbecome covalently coupled to the device surface via the photoreactivegroup. The extent of the covalent coupling may depend on variousfactors, including the amount and reactivity of abstractable hydrogenson the surface and the amount of photoreactive groups that are pendentfrom the hydrophilic photopolymer.

Plastic polymers include those formed of synthetic polymers, includingoligomers, homopolymers, and copolymers resulting from reactions such asaddition or condensation polymerizations. Examples of suitable additionpolymers include, but are not limited to, acrylics such as thosepolymerized from methyl acrylate, methyl methacrylate, hydroxyethylmethacrylate, hydroxyethyl acrylate, acrylic acid, methacrylic acid,glyceryl acrylate, glyceryl methacrylate, methacrylamide, andacrylamide; vinyls such as ethylene, propylene, vinyl chloride, vinylacetate, vinyl pyrrolidone, vinylidene difluoride, and styrene. Examplesof condensation polymers include, but are not limited to, nylons such aspolycaprolactam, polylauryl lactam, polyhexamethylene adipamide,polyhexamethylene dodecanediamide, and also polyurethanes,polycarbonates, polyamides, polysulfones, poly(ethylene terephthalate),polydimethylsiloxanes, and polyetherketone.

Other suitable polymers for the substrate material include polyamides,polyimides, polyolefins, polystyrenes, polyesters, polycarbonates,polyketones, polyureas, acrylonitrile butadiene, butadiene rubber,chlorinated and chloro-sulfonated polyethylene, chloroprene, EPM((poly)ethylene propylene terpolymer), EPDM(ethylene-propylene-dicyclopentadiene copolymer), PE/EPDM blends(polyethylene/ethylene-propylene-dicyclopentadiene copolymer), PP/EPDMblends (polypropylene/ethylene-propylene-dicyclopentadiene copolymer),EVOH (ethylene vinyl alcohol polymer), epichlorihydrin, isobutyleneisoprene, isoprene, polysulfides, silicones, NBR/PVC (acrylonitrilerubber/PVC blend), styrene butadienes, vinyl acetate ethylenes, andcombinations thereof.

In yet other embodiments, the inventive ultra-thin coatings can be usedin conjunction with microfluidic devices. Microfluidic devices aretypically characterized by having one or more fluid channels with atleast one dimension of less than 1 mm. Fluids that are commonly used inmicrofluidic devices include whole blood samples, protein or antibodysolutions, nucleic acid solution, prokaryotic or eukaryotic cellsuspensions, and various buffers. Microfluidic devices having ultra-thinphoto-polymeric coatings can be used in methods to measure variousparameters including fluid viscosity, pH, molecular diffusioncoefficients, chemical binding coefficients, and enzyme reactionkinetics. Microfluidic devices can also be used for flow cytometry, DNAand/or RNA analysis, capillary electrophoresis, isoelectric focusing,immunoassays, sample injection of proteins for analysis via massspectrometry, PCR amplification, cell manipulation, cell separation,cell patterning, and chemical gradient formation. The coated devices canbe used for any form of research, and can also be used in clinicaldiagnostics.

Examples of microfluidic separation devices, particularly chip-based,micromachined capillary electrophoresis (CE) systems are described inU.S. Pat. Nos. 5,904,824, 6,068,752 and 6,103,199.

The use of ultra-thin coatings for microfluidic devices can be verydesirable because the volume of fluids within these channels can be verysmall, for example, in the nanoliter range, and the amount of reagentsand analytes used can also be quite small. In many cases expensivereagents or valuable samples are used in these devices. The ultra-thincoatings of the invention can therefore improve the function of themicrofluidics device by, for example, improving the flow of fluids inthe microfluidics channels, decreasing non-specific absorption ofproteins in the channels, improving the viability of cells in thechannels, and improving chemical separation. These improvements mayresult in a decrease in the quantity of reagents that are needed for acertain process, thereby resulting in savings in overall time and costassociated with any particular microfluidics process.

An ultra-thin coating of photo-polymer can be formed on themicrofluidics channel in the following manner. The device is filled witha coating composition including the hydrophilic polymer havingphotoreactive groups and then the coating composition is treated withirradiation to form an ultra-thin coated layer. Alternately, the coatingcan be formed on the channels prior to assembly of the device.

In yet other embodiments, the inventive coatings can be used inconjunction with biosensors. Biosensors are devices that providemolecular recognition of one or more biological material(s), such asproteins, enzymes, antibodies, DNA, RNA, or microorganisms. Generally,biosensors are useful for identifying and quantifying a target moietyagainst other moieties present in a sample liquid. Specifically, thebiological material included in the sample is quantified by utilizing areaction that is caused when the biological material is recognized by abinding member.

Enzyme biosensors are typically used to detect substances such ascreatinine, glucose, lactic acid, cholesterol, and amino acids, and areutilized for medical diagnostics or in the food industry. A prototypebiosensor is the amperometric glucose sensor. Many enzyme-basedbiosensors operate by promoting the chemical reduction of an electrontransfer agent by the specific reaction of a target component in abiological sample with an enzyme that is specific for the targetcomponent. The amount of biological material (substrate) in a biologicalsample is determined via a quantification apparatus whichelectrochemically measures a reduction quantity of the transfer agent,thereby performing quantitative analysis of the specimen. Biosensors caninclude electrochemical cells in which there can be working electrodes,counter electrodes, and reference electrodes. Biosensors can alsoinclude reactions that promote electrochemiluminescence (ECL) (see, forexample, U.S. Pat. No. 6,852,502).

Electrochemical biosensors are known. They have been used to determinethe concentration of various analytes from biological samples,particularly from blood. Examples of electrochemical biosensors aredescribed in U.S. Pat. Nos. 5,413,690, 5,762,770, 5,798,031, and5,997,817.

The ultra-thin hydrophilic photo-polymeric coatings of the presentinvention can be formed on the surface of the biosensor to improvevarious aspects of the biosensor function, including sensitivity andspecificity.

For example, an ultra-thin coated layer of hydrophilic polymericmaterial can be formed on the hydrophobic surface of a biosensor.Normally, a hydrophobic surface may cause the accumulation of plasmaproteins on the biosensor electrode, leading to denaturing of theproteins and formation of protein deposits. These deposits can affectthe performance of the sensor through physical interference.

The ultra-thin hydrophilic photo-polymeric coatings can reduce theelectrode impedance of the biosensors by allowing the formation of ahydrophilic surface via the ultra-thin photo-polymeric coating, therebypromoting unimpeded water movement on the surface of the sensor.

Furthermore, because the coating is particularly thin, the function ofany binding members on the surface of the device will not besignificantly compromised.

One type of biosensor the ultra-thin hydrophilic polymeric coating canbe formed on is a waveguide sensor, or a biosensor that has waveguidesensor features. Optical waveguide sensors can be used to detect and/ormeasure analytes on a waveguide surface based on the detection of arefractive index change. Planar optical waveguides can function asoptical sensors that detect changes in the media surrounding thewaveguide, as the electromagnetic field propagating in the waveguidewill extend into the surrounding media as an evanescent electromagneticfield. Exemplary waveguide sensors include grating-based waveguidesensors,

Using the methods of the invention, an ultra-thin coating can be formedon the surface of the waveguide, thereby allowing analyte binding tooccur very close to the surface. Since the sensitivity of these types ofdetectors is closely linked to the distance between the surface of thesensor and the bound analyte, an ultra-thin coating of hydrophilicpolymers with attached analyte offers the passivation benefits providedby the properties of the coated hydrophilic polymer while improvingsensitivity by reducing the distance between the waveguide surface andthe bound analyte. Waveguide sensors can be used for various types ofdetection and/or measurement including cells, proteins and peptides,drugs, small organic molecules, such as glucose, nucleic acids, andcarbohydrates.

In yet other embodiments, the ultra-thin hydrophilic photo-polymericcoatings is formed on all or a portion of the surface of a medicalarticle. The medical article can be any that is introduced temporarilyor permanently into a mammal for the prophylaxis or treatment of amedical condition. These devices include any that are introducedsubcutaneously, percutaneously or surgically to rest within an organ,tissue, or lumen of an organ, such as arteries, veins, ventricles, oratria of the heart.

The inventive coating compositions can be utilized to coat virtually anymedical article for which it is desired to provide a functional coatingat a surface thereof. Exemplary medical articles include drug-deliveringvascular stents (e.g., self-expanding stents typically made fromnitinol, balloon-expanded stents typically prepared from stainlesssteel); other vascular devices (e.g., grafts, catheters, valves,artificial hearts, heart assist devices); implantable defibrillators;blood oxygenator devices (e.g., tubing, membranes); surgical devices(e.g., sutures, staples, anastomosis devices, vertebral disks, bonepins, suture anchors, hemostatic barriers, clamps, screws, plates,clips, vascular implants, tissue adhesives and sealants, tissuescaffolds); membranes; cell culture devices; chromatographic supportmaterials; biosensors; shunts for hydrocephalus; wound managementdevices; endoscopic devices; infection control devices; orthopedicdevices (e.g., for joint implants, fracture repairs); dental devices(e.g., dental implants, fracture repair devices), urological devices(e.g., penile, sphincter, urethral, bladder and renal devices, andcatheters); colostomy bag attachment devices; ophthalmic devices;glaucoma drain shunts; synthetic prostheses (e.g., breast); intraocularlenses; respiratory, peripheral cardiovascular, spinal, neurological,dental, ear/nose/throat (e.g., ear drainage tubes); renal devices; anddialysis (e.g., tubing, membranes, grafts).

Other devices include urinary catheters (e.g., surface-coated withantimicrobial agents such as vancomycin or norfloxacin), intravenouscatheters (e.g., treated with antithrombotic agents (e.g., heparin,hirudin, coumadin), small diameter grafts, vascular grafts, artificiallung catheters, atrial septal defect closures, electro-stimulation leadsfor cardiac rhythm management (e.g., pacer leads), glucose sensors(long-term and short-term), degradable coronary stents (e.g.,degradable, non-degradable, peripheral), blood pressure and stent graftcatheters, birth control devices, benign prostate and prostate cancerimplants, bone repair/augmentation devices, breast implants, cartilagerepair devices, dental implants, implanted drug infusion tubes,intravitreal drug delivery devices, nerve regeneration conduits,oncological implants, electrostimulation leads, pain managementimplants, spinal/orthopedic repair devices, wound dressings, embolicprotection filters, abdominal aortic aneurysm grafts, heart valves(e.g., mechanical, polymeric, tissue, percutaneous, carbon, sewingcuff), valve annuloplasty devices, mitral valve repair devices, vascularintervention devices, left ventricle assist devices, neuro aneurysmtreatment coils, neurological catheters, left atrial appendage filters,hemodialysis devices, catheter cuff, anastomotic closures, vascularaccess catheters, cardiac sensors, uterine bleeding patches, urologicalcatheters/stents/implants, in vitro diagnostics, aneurysm exclusiondevices, and neuropatches.

Other devices include, but are not limited to, vena cava filters,urinary dialators, endoscopic surgical tissue extractors, atherectomycatheters, clot extraction catheters, percutaneous transluminalangioplasty catheters (PICA catheters), stylets (vascular andnon-vascular), guidewires (such as coronary guidewires and peripheralguidewires), drug infusion catheters, esophageal stents, circulatorysupport systems, angiographic catheters, transition sheaths anddilators, hemodialysis catheters, neurovascular balloon catheters,tympanostomy vent tubes, cerebro-spinal fluid shunts, defibrillatorleads, percutaneous closure devices, drainage tubes, thoracic cavitysuction drainage catheters, electrophysiology catheters, stroke therapycatheters, abscess drainage catheters, biliary drainage products,dialysis catheters, central venous access catheters, and parentalfeeding catheters.

Other devices suitable for the present invention include, but are notlimited to, implantable vascular access ports, blood storage bags, bloodtubing, intraaortic balloon pumps, cardiovascular sutures, totalartificial hearts and ventricular assist pumps, extracorporeal devicessuch as blood oxygenators, blood filters, hemodialysis units,hemoperfusion units, plasmapheresis units, hybrid artificial organs suchas pancreas or liver and artificial lungs, as well as filters adaptedfor deployment in a blood vessel in order to trap emboli (also known as“distal protection devices”).

An ultra-thin hydrophilic photo-polymeric coating of the invention canbe particularly useful for those medical devices that will come incontact with aqueous systems, such as bodily fluids. In some aspects, anultra-thin hydrophilic layer improves the biocompatibility of the devicesurface and can minimize adverse reactions that may impair function ofthe coated device in the body.

The ultra-thin hydrophilic photo-polymeric coating is formed using ahydrophilic polymer having pendent photoreactive groups. The hydrophilicpolymer that is used to form the ultra-thin layer, for example, can be acopolymer or a homopolymer. As used herein, the term “hydrophilic”refers to a polymer that does not repel water molecules. Hydrophilicpolymers typically are soluble in water.

The hydrophilic polymer that is used to form the ultra-thin coating canbe a synthetic polymer, a natural polymer, or a derivative of a naturalpolymer. Exemplary natural hydrophilic polymers includecarboxymethylcellulose, hydroxymethylcellulose, derivatives of thesepolymers, and similar natural hydrophilic polymers and derivativesthereof.

In some embodiments the hydrophilic polymer that includes pendentphotoreactive groups is synthetic. Synthetic hydrophilic polymers can beprepared from any suitable monomer including acrylic monomers, vinylmonomers, ether monomers, or combinations of any one or more of thesetypes of monomers. Acrylic monomers include, for example, methacrylate,methyl methacrylate, hydroxyethyl methacrylate, hydroxyethyl acrylate,methacrylic acid, acrylic acid, glycerol acrylate, glycerolmethacrylate, acrylamide, methacrylamide, and derivatives and/ormixtures of any of these. Vinyl monomers include, for example, vinylacetate, vinylpyrrolidone, vinyl alcohol, and derivatives of any ofthese. Ether monomers include, for example, ethylene oxide, propyleneoxide, butylene oxide, and derivatives of any of these. Examples ofpolymers that can be formed from these monomers includepoly(acrylamide), poly(methacrylamide), poly(vinylpyrrolidone),poly(acrylic acid), poly(ethylene glycol), poly(vinyl alcohol), andpoly(HEMA). Examples of hydrophilic copolymers include, for example,methyl vinyl ether/maleic anhydride copolymers and vinylpyrrolidone/(meth)acrylamide copolymers. Mixtures of homopolymers and/orcopolymers can be used.

In some embodiments, the hydrophilic photo-polymer is a vinylpyrrolidone polymer, or a vinyl pyrrolidone/(meth)acrylamide copolymersuch as poly(vinylpyrrolidone-co-methacrylamide). If a PVP copolymer isused, it can be a copolymer of vinylpyrrolidone and a monomer selectedfrom the group of hydrophilic monomers. Exemplary hydrophilic monomersinclude (meth)acrylamide and (meth)acrylamide derivatives, such asalkyl(meth)acrylamide and aminoalkyl(meth)acrylamide, such asaminopropylmethacrylamide and dimethylaminopropylmethacrylamide. Use ofPVP copolymers is particularly advantageous for the preparation and useof PVP that is derivatized with photoreactive groups.

Vinyl pyrrolidone copolymers can be prepared in order to provide aphoto-polymer with a specific property. For example,poly(vinylpyrrolidone-co-vinyl acetate) polymers can be prepared toalter their relative hydrophilicity, and to change the properties of thefilm in accordance with its desired use.

Methods for the preparation of PVP as well as photo-PVP are known in theart (see U.S. Pat. No. 6,077,698). PVP can be prepared by thepolymerization of 1-vinyl-2-pyrrolidone in water using hydrogen peroxideas an initiator. Methods for terminating the polymerization VP can allowthe preparation of PVP of desired molecular weights.

According to the invention, it has also been discovered that polymershaving a molecular weight of about 500 KDa or less are able to provide avery effective ultra-thin hydrophilic coating. That is, hydrophilicpolymers of this size can be formed into an ultra-thin coating havingproperties in accordance with preferred embodiments of the invention,such as wettability and durability. In some aspects, the hydrophilicpolymers of the invention have a weight average molecular weight (M_(w))size in the range of about 10 kDa to about 100 kDa, and in other aspectsin the range of about 10 kDa to about 75 kDa.

As used herein “weight average molecular weight” or M_(w), is anabsolute method of measuring molecular weight and is particularly usefulfor measuring the molecular weight of a polymer, such as a preparationsof photo-polymers as described herein. Polymer preparations typicallyinclude polymers that individually have minor variations in molecularweight. Polymers are molecules that have a relatively high molecularweight and such minor variations within the polymer preparation do notaffect the overall properties of the polymer preparation (for example,the characteristics of a photo-polymer preparation). The weight averagemolecular weight (M_(w)) can be defined by the following formula:

$M_{w} = \frac{\sum\limits_{i}^{\;}{N_{i}M_{i}^{2}}}{\sum\limits_{i}^{\;}{N_{i}M_{i}}}$

wherein N represents the number of moles of a polymer in the sample witha mass of M, and Σ_(i) is the sum of all N_(i)M_(i) (species) in apreparation. The M_(w) can be measured using common techniques, such aslight scattering or ultracentrifugation. Discussion of M_(w) and otherterms used to define the molecular weight of polymer preparations can befound in, for example, Allcock, H. R. and Lampe, F. W., ContemporaryPolymer Chemistry; pg 271 (1990).

In another embodiment of the invention the ultra-thin hydrophilicphoto-polymeric layer is formed from a coating composition that includestwo or more hydrophilic polymers, at least one of which has pendentphotoreactive groups. Optionally, the ultra-thin layer can be formedfrom a coating composition that includes two hydrophilic photo-polymers.In some aspects at least one of the two hydrophilic polymers ispoly(vinylpyrrolidone).

If two or more hydrophilic polymers are used in the coating composition,in some aspects, at least one of the polymers has a M_(w) of about 500kDa or less, or in the range of about 10 kDa to about 500 kDa. If two ormore hydrophilic polymers are used in the coating composition, in someaspects both have a M_(w) of about 500 kDa or less, or in the range ofabout 10 kDa to about 500 kDa.

Photoreactive groups are pendent from the hydrophilic polymer and areactivated during the coating process in order to form the ultra-thincoating. Generally, a photoreactive group that is “pendent” from thehydrophilic polymer is arranged on the polymer in a manner so that itcan be activated using light energy and bond to a moiety, such as aphoto-polymer and/or a substrate material.

The photoreactive groups can be pendent along the length of the polymerand spaced along the length of the polymer in a random or orderedmanner. It is speculated that photoreactive groups spaced along thelength of the polymer allow the photo-polymer to associate with thesurface prior to irradiation in a manner that promotes the formation ofan ultra thin coatings according to the methods described herein.

Photoreactive groups, broadly defined, are groups that respond tospecific applied external light energy to undergo active speciegeneration with resultant covalent bonding to a target. Photoreactivegroups are those groups of atoms in a molecule that retain theircovalent bonds unchanged under conditions of storage but which, uponactivation, form covalent bonds with other molecules. The photoreactivegroups generate active species such as free radicals, nitrenes,carbenes, and excited states of ketones upon absorption of externalelectromagnetic or kinetic (thermal) energy. Photoreactive groups may bechosen to be responsive to various portions of the electromagneticspectrum, and photoreactive groups that are responsive to ultraviolet,visible or infrared portions of the spectrum are preferred.Photoreactive groups, including those that are described herein, arewell known in the art. The present invention contemplates the use of anysuitable photoreactive group for formation of the inventive coatings asdescribed herein.

Photoreactive groups can generate active species such as free radicalsand particularly nitrenes, carbenes, and excited states of ketones, uponabsorption of electromagnetic energy. Photoreactive groups can be chosento be responsive to various portions of the electromagnetic spectrum.Those that are responsive to the ultraviolet and visible portions of thespectrum are typically used.

Photoreactive aryl ketones such as acetophenone, benzophenone,anthraquinone, anthrone, and anthrone-like heterocycles (for example,heterocyclic analogs of anthrone such as those having nitrogen, oxygen,or sulfur in the 10-position), or their substituted (for example, ringsubstituted) derivatives can be used. Examples of aryl ketones includeheterocyclic derivatives of anthrone, including acridone, xanthone, andthioxanthone, and their ring substituted derivatives. Some photoreactivegroups include thioxanthone, and its derivatives, having excitationenergies greater than about 360 nm.

These types of photoreactive groups, such as aryl ketones, are readilycapable of undergoing the activation/inactivation/reactivation cycledescribed herein. Benzophenone is a particularly preferred photoreactivegroup, since it is capable of photochemical excitation with the initialformation of an excited singlet state that undergoes intersystemcrossing to the triplet state. The excited triplet state can insert intocarbon-hydrogen bonds by abstraction of a hydrogen atom (from a supportsurface, for example), thus creating a radical pair. Subsequent collapseof the radical pair leads to formation of a new carbon-carbon bond. If areactive bond (for example, carbon-hydrogen) is not available forbonding, the ultraviolet light-induced excitation of the benzophenonegroup is reversible and the molecule returns to ground state energylevel upon removal of the energy source. Photoactivatable aryl ketonessuch as benzophenone and acetophenone are of particular importanceinasmuch as these groups are subject to multiple reactivation in waterand hence provide increased coating efficiency.

The azides constitute another class of photoreactive groups and includearylazides (C6R5N3) such as phenyl azide and 4-fluoro-3-nitrophenylazide; acyl azides (—CO—N₃) such as benzoyl azide and p-methylbenzoylazide; azido formates (—O—CO—N₃) such as ethyl azidoformate and phenylazidoformate; sulfonyl azides (—SO₂—N₃) such as benezensulfonyl azide;and phosphoryl azides [(RO)₂PON₃] such as diphenyl phosphoryl azide anddiethyl phosphoryl azide.

Diazo compounds constitute another class of photoreactive groups andinclude diazoalkanes (—CHN₂) such as diazomethane anddiphenyldiazomethane; diazoketones (—CO—CHN₂) such as diazoacetophenoneand 1-trifluoromethyl-1-diazo-2-pentanone; diazoacetates (—O—CO—CHN₂)such as t-butyl diazoacetate and phenyl diazoacetate; andbeta-keto-alpha-diazoacetatoacetates (—CO—CN₂CO—O—) such as t-butylalpha diazoacetoacetate.

Other photoreactive groups include the diazirines (—CHN₂) such as3-trifluoromethyl-3-phenyldiazirine; and ketenes (CH═C═O) such as keteneand diphenylketene.

A hydrophilic photo-polymer can be formed using any sort of syntheticprocess that will result in the formation of a hydrophilic polymer withone or more pendent photoreactive groups. For example, a hydrophilicphoto-polymer can be synthesized by attaching photoreactive groups to a“preformed” hydrophilic polymer. The preformed polymer can be obtainedfrom a commercial source or be synthesized from the polymerization of adesired monomer or combination of different monomers. In one example ofpreparing the photopolymer, a compound that includes a photoreactivegroup and a first reactive group is reacted with a portion of ahydrophilic polymer that is reactive with the first reactive group,resulting in the formation of a hydrophilic polymer having a pendentphotoreactive group. The reaction preferably does not result in theactivation of the photoreactive group; therefore the photoreactive groupremains “latent” and capable of activation by actinic radiation duringthe coating process. Such attachments of the photoreactive group can beachieved by, for example, substitution or addition reactions.

For example, in one embodiment, the polymeric portion of thephoto-polymer is formed by reacting acrylamide,2-acrylamide-2-methylpropane sulfonic acid, and N-(3-aminopropyl)methacrylamide. In another embodiment, the polymeric portion is preparedby the copolymerization of 1-vinyl-2-pyrrolidone and N-(3-aminopropyl)methacrylamide. The copolymers are derivatized with an acyl chloride(such as, for example, 4-benzoylbenzoyl chloride) under Schotten-Baumannconditions to form photo-poly(vinylpyrrolidone) (also referred to as“photo-PVP”). That is, the acyl chloride reacts with the amino group ofthe N-(3-aminopropyl) moiety of the copolymer. An amide is formedresulting in the attachment of the aryl ketone to the polymer. Theliberated hydrochloric acid is neutralized with an aqueous basesolution.

In another method of preparing the photopolymer, monomers havingphotoreactive groups are obtained or prepared. These monomers are thenco-polymerized with other monomers that do not have photoreactive groupsto create a photopolymer. This is a particularly suitable way forpreparing photopolymers that have desired amount of photoreactivegroups, and desired monomeric units. A useful polymerizable mixture ofmonomers for preparation of the photopolymer includes, for example, fromabout 0.1% to about 10% of a photoreactive group-monomer, and from about90% to about 99.9% of a hydrophilic monomer, or combination ofhydrophilic monomers, as based on a molar percentage of the total amountof monomers present in the mixture. The photo monomers used to preparethe photopolymer can include any suitable polymerizable portion, suchas, for example, acrylic monomers, vinyl monomers, or ether monomers.

In one exemplary method of synthesis, photo-polyacrylamide is preparedby copolymerizing methacrylamide having a photoreactive group withacrylamide. The photo-methacrylamide monomer can be prepared accordingto the process described in U.S. Pat. No. 6,007,833 (see Examples 1 &2). Specifically, a methacrylamide-oxothioxanthene monomer(N-[3-(7-methyl-9-oxothioxanthene-3-carboxamido) propyl]methacrylamide(MTA-APMA)) can be prepared by reacting7-methyl-9-oxothioxanthene-3-carboxylic acid chloride (MTA-Cl) withN-(3-aminopropyl)methacrylamide hydrochloride (APMA). MTA-APMA can thenbe copolymerized with acrylamide in DMSO in the presence of a chaintransfer agent, a co-catalyst, and a free radical initiator. MTA-APMAcan also be copolymerized with other types of monomers, such as vinylpyrrolidone, to produce other photo-polymers (see also U.S. Pat. No.6,007,833).

In order to provide a substrate with an ultra-thin hydrophilicphoto-polymeric coated layer, the hydrophilic photo-polymer is providedin a coating composition. The coating composition is then used inconjunction with a substrate to be coated to form the ultra-thin layer.In many aspects of the invention, the coating composition is placed incontact with a surface of an article to be coated and then thecomposition and target surface of the article is irradiated to activatethe photoreactive groups of the photo-polymer to form the coated layer.

The coating methods described herein can be performed a number of ways,but generally, the formation of the ultra-thin layer includes an“in-solution” step wherein the coating composition contacts thesubstrate and then treated with irradiation to form the coating. Forexample, a coating solution is placed in contact with the surface of asubstrate and then the substrate is irradiated before any significantportion of the composition is lost through evaporation of the liquidcomponent of the composition.

The surface of the substrate can optionally be pre-treated prior tobeing placed in contact with the coating composition. In many cases thepre-treatment can facilitate the step wherein the coating composition isplaced in contact with the surface. For example, all or a portion of thehydrophobic surface can be pre-wetted with a water miscible solvent suchas an alcohol. Pre-wetting can be performed for any period of time, butgenerally, a short period of pre-wetting (seconds) is sufficient. Forexample, with a filter, pre-wetting can be performed by drawing thepre-wetting fluid through the filter under vacuum.

In the least, the coating composition includes the hydrophilicphoto-polymer in a suitable liquid; other components can be optionallyadded. A coating composition can be prepared by dissolving aphoto-polymer in a coating liquid, wherein the photo-polymer is presentat a concentration sufficient by itself or in conjunction with othercoating materials, to form the ultra-thin coated layer on the surface ofthe substrate. For example, in many embodiments the photo-polymer can bedissolved at a concentration in the range of about 0.01 to about 50mg/mL. One photo-polymer, more than one photo-polymer, or a combinationof one or more photo-polymers with one or more non-photo polymers can becombined to provide a coating composition with a polymer concentrationin this range. More specific exemplary ranges are from about 0.1 mg/mLto about 10 mg/mL, and from about 0.5 mg/mL to about 5.0 mg/mL. Forexample, and as demonstrated herein, compositions includingphoto-poly(acrylamide), or photo-poly(acrylamide) and a non-photopolymer, were prepared at a concentration of 1 mg/mL and used to form anultra-thin polymeric coating.

Suitable liquids for the coating composition can be aqueous liquids,non-aqueous liquids, or mixtures thereof. The term “aqueous” indicatesthat the main component of the liquid is water. However, an aqueousliquid could have significant concentrations of other dissolved liquids,for example, water soluble liquids such as alcohols, acetone, diluteacids, etc. Specific examples include, diethylene glycol, methanol,ethanol, n-propanol, isopropanol (IPA), n-butanol, n-hexanol,2-pyrrolidone, polyethylene glycol, propylene glycol, 1,4-butanediol,glycerol, triethanolamine, propionic acid, and acetic acid. An aqueoussolution can also be basic or acidic, and can include any sort ofsuitable salt. In some cases, one or more salts can be included in thecoating composition to promote the association of the photo-polymer withthe hydrophobic surface.

The ultra-thin coating can be formed in many different ways. In somecases it may be desired to form an ultra-thin coated layer over theentire surface of the substrate. This can be performed by obtaining aliquid coating composition, immersing the substrate in the coatingcomposition, and then irradiating the substrate over its entire surfaceto form an ultra-thin coated layer. Either or both the position of thesubstrate or the position of the light source can be adjusted to provideactivating irradiation over the surface of the device, if necessary.

Another way of performing the coating process is to apply the coatingcomposition to a portion of the surface of the substrate. For example, adrop of coating composition can be applied to a portion of the device tobe coated, and then the device is irradiated, forming a coating only onthe portion of the device that is in contact with the coatingcomposition. For example, in the case that one surface of an electrodeis to be coated, the coating composition can be applied to that surfaceand then the surface irradiated to form the ultra-thin coated layer.Surface tensions of the coating composition may allow the drop ofcoating composition to cover the entire surface of one side of theelectrode.

In some cases, a temporary barrier may be created on the substratesurface to contain the coating composition and define the area that theultra-thin coating is to be formed on. This can be useful for creatingultra-thin coatings on surfaces wherein a pattern, or more than onepattern, of coated polymer is desired.

In other cases, if the ultra-thin coating is to be formed on a portionof a substrate, light irradiation can be directed to that portion of thesubstrate to activate the photoreactive groups thereby promotingformation of the coating.

The step of activating the photo-groups to promote the formation of theultra-thin coating is typically performed by using a source ofirradiation (light source) sufficient to activate the photoreactivegroups of the photopolymer. For example, the photoreactive groups canhave activation wavelengths in the UV and visible portions of thespectrum, such as in the range of 100-700 nm, or 300-600 nm, or 200-400nm, or 300 -340 nm. Light sources typically used to activatephoto-polymers provide a source of UV irradiation, such as shortwavelength UV. Preferred photoreactive groups are activated by UVradiation in the range of 330 nm to 340 nm. Light sources that provideoutput radiation sufficient to activate the photoreactive groups andpromote formation of the coating can be used. Suitable light sources canincorporate, for example, metal halide bulbs, or other suitable bulbsthat provide an activating source of irradiation. One suitable lightsource is a Dymax BlueWave™ Spot Cure System, which is commerciallyavailable from Dymax Corp. (Torrington, Conn.).

Generally, the ultra-thin coating is formed by “in-solution” irradiationof the substrate. In this method light travels through the solution tothe surface of the device wherein the light activates the photoreactivegroups of the photopolymers that are proximal to the surface of thedevice, promoting bond formation and formation of the ultra-thin coatedlayer. While any amount of coating solution can be covering a surface ofthe substrate intended to be coated, in order to most efficientlypromote formation of the ultra-thin layer, one can minimize the distancethat light needs to travel through the solution by controlling theamount of coating solution covering the surface of the substrate. Forexample, a standard amount of solution covering the surface of thedevice could be in the range of 1 mm to 10 mm in depth.

The amount of energy that is applied to the surface can vary dependingon a number of factors, including the type and amount of photo-polymerused, the substrate material, and the type and amount of coatingcomposition. In some aspects an amount of energy in the range of about 5mJ/cm²to about 5000 mJ/cm² as measured at 335 nm, is applied to thesurface; a more preferable range is from about 50 mJ/cm² to about 500mJ/cm². Other ranges can be used in conjunction with the step of formingthe coating.

After the substrate has been irradiated to form the ultra thin layer,the remaining coating composition can be removed, or the coatingcomposition can be washed off using a wash solution.

In another aspect of the invention, a water-soluble crosslinking agenthaving pendent photoreactive groups can be used in methods for formingthe ultra-thin coated layer. The crosslinking agent can be added toimprove properties of the coating, such as durability. In forming theultra-thin coating, the crosslinking agent can provide additionalbonding between the hydrophilic polymers of the ultra-thin coated layer,thereby improving its durability.

In some aspects, the coating can be formed by including a water-solublecrosslinking agent having pendent photoreactive groups in the coatingcomposition along with the hydrophilic polymer having pendentphotoreactive groups. Alternatively, the water-soluble crosslinkingagent can be used independently of the hydrophilic polymer to form theultra-thin coated layer.

In some aspects, a coating composition is prepared that includes ahydrophilic polymer having pendent photoreactive groups and a watersoluble crosslinking agent.

A substrate is then contacted with the coating composition having atleast these two components, for example, by immersing the substrate inthe coating composition. The composition and substrate can then beirradiated to form the ultra-thin coated layer.

Alternatively, the crosslinking agent can be placed in contact with thesubstrate after the substrate has been in contact with the hydrophilicphoto-polymer. For example, the ultra-thin coating can be prepared byfirst contacting a substrate with a first coating composition thatincludes a hydrophilic polymer having pendent photoreactive groups; thecoating composition is then treated to activate the photoreactive groupsof the hydrophilic photo-polymer. Full or partial activation of thephotoreactive groups can be performed. Optionally, one or more washingsteps can be performed before the second coating composition iscontacted to the substrate. After the step of irradiation, the firstcoating composition can be removed and a second coating composition thatincludes the crosslinking agent can be placed in contact with thesubstrate. Irradiation of the second coating composition and thesubstrate can then be performed.

Alternatively, after the first coating composition is irradiated, thecrosslinking agent can be added to the first coating composition, andthen a second irradiation step can be performed. In this aspect, theultra-thin coated layer is formed after the first irradiation step, andthe addition and subsequent irradiation of the crosslinking agentfurther crosslinks the ultra-thin coated layer. In some aspects, thismethod may save time and reagents, as various steps, washings, and/orcompositions can be optionally eliminated.

Exemplary water-soluble cross-linking agents having photoreactive groupsinclude ionic crosslinkers. Any suitable ionic photoactivatablecross-linking agent can be used. In some embodiments, the ionicphotoactivatable cross-linking agent is a compound of formula I:

X₁—Y—X₂

where Y is a radical containing at least one acidic group, basic group,or a salt of an acidic group or basic group. X₁ and X₂ are eachindependently a radical containing a latent photoreactive group.

The photoreactive groups can be the same as those described for use withthe hydrophilic polymer. Spacers can also be part of X₁ or X₂ along withthe latent photoreactive group. In some embodiments, the latentphotoreactive group includes an aryl ketone or a quinone.

The radical Y in formula I provides the desired water solubility for theionic photoactivatable cross-linking agent. The water solubility (atroom temperature and optimal pH) is at least about 0.05 mg/ml. In someembodiments, the solubility is about 0.1 to about 10 mg/ml or about 1 toabout 5 mg/ml.

In some embodiments of formula I, Y is a radical containing at least oneacidic group or salt thereof. Such a photoactivatable cross-linkingagent can be anionic depending upon the pH of the coating composition.Suitable acidic groups include, for example, sulfonic acids, carboxylicacids, phosphonic acids, and the like. Suitable salts of such groupsinclude, for example, sulfonate, carboxylate, and phosphate salts. Insome embodiments, the ionic cross-linking agent includes a sulfonic acidor sulfonate group. Suitable counter ions include alkali, alkalineearths metals, ammonium, protonated amines, and the like.

For example, a compound of formula I can have a radical Y that containsa sulfonic acid or sulfonate group; X₁ and X₂ can contain photoreactivegroups such as aryl ketones. Such compounds include4,5-bis(4-benzoylphenylmethyleneoxy) benzene-1,3-disulfonic acid orsalt; 2,5-bis(4-benzoylphenylmethyleneoxy)benzene-1,4-disulfonic acid orsalt; 2,5-bis(4-benzoylmethyleneoxy)benzene-1-sulfonic acid or salt;N,N-bis[2-(4-benzoylbenzyloxy)ethyl]-2-aminoethanesulfonic acid or salt,and the like. See U.S. Pat. No. 6,278,018. The counter ion of the saltcan be, for example, ammonium or an alkali metal such as sodium,potassium, or lithium.

In other embodiments of formula I, Y can be a radical that contains abasic group or a salt thereof. Such Y radicals can include, for example,an ammonium, a phosphonium, or a sulfonium group. The group can beneutral or positively charged, depending upon the pH of the coatingcomposition. In some embodiments, the radical Y includes an ammoniumgroup. Suitable counter ions include, for example, carboxylates,halides, sulfate, and phosphate.

For example, compounds of formula I can have a Y radical that containsan ammonium group; X₁ and X₂ can contain photoreactive groups thatinclude aryl ketones. Such photoactivatable cross-linking agents includeethylenebis(4-benzoylbenzyldimethylammonium) salt; hexamethylenebis(4-benzoylbenzyldimethylammmonium) salt;1,4-bis(4-benzoylbenzyl)-1,4-dimethylpiperazinediium) salt,bis(4-benzoylbenzyl)hexamethylenetetraminediium salt,bis[2-(4-benzoylbenzyldimethylammonio)ethyl]-4-benzoylbenzylmethylammoniumsalt; 4,4-bis(4-benzoylbenzyl)morpholinium salt;ethylenebis[(2-(4-benzoylbenzyldimethylammonio)ethyl)-4-benzoylbenzylmethylammonium]salt; and 1,1,4,4-tetrakis (4-benzoylbenzyl)piperzinediium salt. SeeU.S. Pat. No. 5,714,360. The counter ion is typically a carboxylate ionor a halide. On one embodiment, the halide is bromide.

After the ultra-thin coated layer has been formed on the surface of thedevice, it includes hydrophilic polymer having pendent photo-“reacted”groups, meaning that photoreactive groups had undergone activation andreaction with a target moiety, for example another hydrophilic polymerand/or the substrate surface, to form a covalent bond to immobilize thepolymer.

The invention will be further described with reference to the followingnon-limiting Examples.

EXAMPLES Preparation of Photopolymers

Photo-polyacrylamide (photo-PA) was prepared by copolymerizing amethacrylamide having a photoreactive group with acrylamide. Thephotoreactive monomer, N-[3-(4-Benzoylbenzamido)propyl]methacrylamide,was prepared according to the process described in U.S. Pat. No.5,858,653 (see Example 3).

Photo-poly(vinylpyrrolidone) (photo-PVP) was made by thecopolymerization of 1-vinyl-2-pyrrolidone (Aldrich) andN-(3-aminopropyl) methacrylamide (APMA), followed by photoderivatizationof the polymer using 4- benzoylbenzoyl chloride, as described in Example22 of U.S. Pat. No. 6,077,698, under Sehotten-Baumann conditions (a twophase aqueous/organic reaction system). APMA was prepared as describedin Example 2 of U.S. Pat. No. 5,858,653.

Example 1

A thin photo-polymer coating was formed on a hydrophobic substratehaving small pores. Specifically, expanded PTFE (ePTFE) membranes werecoated with photo-polyacrylamide to provide a very thin hydrophiliccoating over the membrane material. An expanded PTFE membrane having a0.2 micron (average) pore size and 47 mm diameter (Donaldson, Inc.,Minneapolis, Minn.) was wetted with 2 mL isopropanol two times for a fewseconds at room temperature. Excess isopropanol was removed with anaspirator vacuum after each wetting. Photo-PA (30-50 kDa MW) (SurModics,Inc., Eden Prairie, Minn.) was prepared at a concentration of 1 mg/mL inwater, and 2 mL of the photo-PA solution were pulled quickly (2 sec)through the ePTFE membrane under vacuum. The vacuum process was repeatedan additional three times, but with 4 mL of photo-PA solution at eachtime. The ePTFE membrane was then immersed in 4 mL of the photo-PAsolution leaving approximately 1 mm of solution covering the membraneand illuminated for 60 seconds using an ultraviolet Dymax™ Cure System(light system commercially available from Dymax; Torrington, Conn.) at adistance of 20 cm. This distance and time provided the membrane withapproximately 100 mJ/cm² in the wavelength range 330-340 nm. Duringillumination, the membrane was kept wet and not allowed to dry. Afterillumination, the membrane was removed from the photo-PA solution,washed with water by vacuum, and dried at 55° C. for 15 minutes. Thecoated membrane demonstrated complete rewetting when immersed in water(as compared to the un-coated membranes), indicating the presence of aphoto-PA coating on the membrane.

The photo-PA-coated ePTFE membrane was imaged using scanning electronmicrography (SEM) and compared to an ePTFE membrane having polymercoating. The membranes were imaged at 10k × at using an acceleratingvoltage of 0.85 kV. The SEM micrographs show that the membrane size ofthe photo-PA coated ePTFE membrane and the uncoated membrane aresubstantially the same.

Example 2

The photo-PA-coated ePTFE membrane as prepared in Example 1 was testedto determine its affect on the flow of water (flux).

Flux was measured using an aspirator vacuum at a pressure of 100 mm. Hg(0.13 ATM). 10 mL of water was placed on the coated membrane and thevacuum was applied to draw the water through the coated membrane. 10 mLof water was completely pulled through the membrane in 17 seconds.Following this, an additional 100 mL of water was pulled through themembrane under vacuum, and then the membrane was allowed to dry. Afterdrying, an additional 10 mL of water was pulled through the filter underthe same vacuum. This time, the 10 mL of water was completely pulledthrough the membrane in 10 seconds. Water could not be drawn through anuncoated membrane using the pressure as indicated above.

Example 3

Wetting and coating of the ePTFE membrane was performed as described inExample 1 except that the coating composition was a mixture ofphoto-polyacrylamide at a concentration of 0.95 mg/mL andpolyvinylpyrrolidone (Kollidon™ 30, BASF; PVP) at a concentration of0.05 mg/mL in water. After illumination, the membrane was removed fromthe photo-PA/PVP solution, washed with water by vacuum, and dried at120° C. for 15 minutes. The photo-PA/PVP-coated membranes werecompletely wettable after drying at 120° C.

The photo-PA/PVP-coated ePTFE membrane was imaged using scanningelectron micrography (SEM) as described in Example 1. The SEMmicrographs show that the membrane size of the photo-PA/PVP-coated ePTFEmembrane and the uncoated membrane are substantially the same, furtherindicating that the coating on the membrane held up well to highertemperatures. Use of a higher temperature also indicates that the coatedmembrane can be heat sterilized without loss of the hydrophilicproperties of the coating.

Example 4

The photo-PA/PVP-coated ePTFE membrane as prepared in Example 3 wastested to determine its affect on the flow of water (flux).

Flux was measured according the process carried out in Example 2. 10 mLof water was completely pulled through the membrane in 20 seconds.

Example 5

Wetting and coating of the ePTFE membrane was performed as described inExample 1 except that the coating composition was a mixture ofphoto-polyacrylamide at a concentration of 0.95 mg/mL and photo-PVP at aconcentration of 0.05 mg/mL in water. The membranes were also washed anddried as detailed in Example 3. The photo-PA/photo-PVP-coated membraneswere completely wettable after drying at 120° C. This membrane was alsotested to determine its affect on the flow of water.

Example 6

A polypropylene substrate provided with an ultra thin coating ofphoto-PVP and then tested for the ability of the coating to wick water.A 50 mm thick melt blown polypropylene (Daramic Corp., Owensboro, Ky.)was saturated with a solution of photo-PVP at 1 mg/mL in a 99.4%water/0.6% hexanol V/V mixture. The saturated material was illuminatedfor 1 minute under a Dymax™ light, removed from the coating solution,and then allowed to dry. The resulting material was permanently wettablewith water as demonstrated by its ability to wick water repeatedly. Thismaterial wicks water to the height of 1 inch in 10 seconds.

Wicking was compared to polypropylene substrates that were irradiatedafter (post-solution irradiation) the polypropylene was dipcoated in thephoto-deviratized polyvinylpyrrolidone solution. In this case, thecoating solution that was dip-coated on to the polypropylene was allowedto dry before illumination. For these post-solution irradiated samples,the coated substrates did not wick water.

Example 7

The hydrophilic photo-polymer coatings were examined by atomic forcemicroscopy to determine their thickness.

Soda lime glass microscope slides (Erie Scientific, Portsmouth, N.H.)were silane treated by dipping in a mixture ofp-tolyldimethylchlorosilane (1% w/v) and n-decyldimethylchlorosilane (1%w/v; United Chemical Technologies, Bristol, Pa.) in acetone. After airdrying, the slides were cured at 120° C. for 1 hour. Slides were thenwashed with acetone followed by dipping in DI water and drying. Theslides were submerged to a depth of approximately 1 mm in a solution ofeither photo-PA or photo-PVP at 1 mg/mL in water and illuminated for 1minute under a Dymax lamp to deliver approximately 100 mJ/cm².

Slides were washed with water and spun dry in a centrifuge. Presence ofthe coating was ascertained by water contact angle using a Kruss DSA 10goniometer (Hamburg, Germany). The base silane had a contact angle of72.8±0.4°. The photo-PA coating was 17.5±2.4° and the photo-PVP was25.1±3.7°. The thickness of these coatings was measured by atomic forcemicroscopy (AFM). The coating was cut using a brass blade and theresulting step height measured using contact mode AFM. Thephoto-poly(acrylamide) was measured at 2.4±0.5 nm and the photo-PVP at1.5±0.3 nm. Errors are standard deviation.

1. A method for forming a hydrophilic polymeric coating having athickness of 20 nm or less on a surface of a substrate, the methodcomprising steps of: (a) contacting the substrate with a liquid coatingcomposition comprising a hydrophilic polymer comprising at least onependent latent photoreactive group; and while the liquid coatingcomposition is in contact with the substrate, (b) irradiating thecomposition to activate the photoreactive groups to form the hydrophilicpolymeric coating having a thickness of 20 nm or less.
 2. The method ofclaim 1 wherein the hydrophilic polymeric coating has a thickness of 5nm or less.
 3. The method of claim 1 wherein the step of irradiating thephotoreactive groups are activated by radiation having a wavelength inthe range of 200 mu to 400 nm.
 4. The method of claim 1 wherein the stepof irradiating the photoreactive groups are activated by UV radiation inan amount in the range of 5 mJ/cm2 to 5000 mJ/cm2.
 5. The method ofclaim 5 wherein the photoreactive group comprises an aryl ketoneselected from the group consisting of acetophenone, benzophenone,anthraquinone, anthrone, anthrone-like heterocycles, and substitutedderivatives thereof.
 6. The method of claim 1 wherein the substrate isselected from the group of articles having fibers, pores, filaments,threads, processes, or apertures, or combinations thereof.
 7. The methodof claim 1 wherein the substrate is selected from the group consistingof silicon materials, silver surfaces having organic molecules,chemically stable semiconductor layers, cluster/molecule/semiconductorassemblies, cluster networks, micro-electro-mechanical-systems (MEMS),actuators, micro- and nano-scale integrated systems, micro-fluidicbio-chips, micro-flow systems, and nano-electronic devices for DNAcharacterization.
 8. The method of claim 1 wherein the substratecomprises an implantable medical device.
 9. The method of claim 8wherein the implantable medical device comprises a catheter.
 10. Themethod of claim 1 wherein the liquid coating composition is placed incontact with a substrate having a hydrophobic surface and that is a poorsource of, or provides no abstractable hydrogens.
 11. The method ofclaim 1 wherein the hydrophilic polymer has a molecular weight of 500kDa or less.
 12. The method of claim 22 wherein the hydrophilic polymerhas a molecular weight in the range of 10 kDa to 500 kDa.
 13. The methodof claim 1 wherein the hydrophilic polymer is present in the liquidcoating composition at a concentration in the range of 0.01 mg/mL to 50mg/mL.
 14. The method of claim 1 comprising a step a wetting thesubstrate with alcohol prior to the step of contacting.
 15. The methodof claim 1 wherein the liquid coating composition is an aqueouscomposition.
 16. An implantable medical device having a hydrophilicpolymeric coating having a thickness of 20 nm or less, the coatingcomprising a plurality of hydrophilic polymers covalently bonded viapendent photo-reactive groups; wherein the pendent photo-reactive groupshave been reacted to form the hydrophilic polymeric coating; and whereinthe coating is formed by a process comprising contacting an implantablemedical device with a liquid coating composition comprising ahydrophilic polymer comprising at least one pendent latent photoreactivegroup, and while the coating composition is in contact with the device,irradiating the composition to activate the pendent latent photoreactivegroups to form the hydrophilic polymeric coating.
 17. The device ofclaim 16 wherein the photoreactive group is attached to the hydrophilicpolymer via an amide bond.
 18. The device of claim 16 wherein thehydrophilic polymer comprises aminoalkyl(meth)acrylamide and thephotoreactive group is attached to the polymer via theaminoalkyl(meth)acrylamide.
 19. The device of claim 16 wherein thehydrophilic polymer comprises from a photoreactive group-monomer in anamount in a range from 0.1% to about 10%, and a hydrophilic monomer, orcombination of hydrophilic monomers, in an amount in a range from 90% toabout 99.9%, as based on a molar percentage.
 20. An implantable medicaldevice having a hydrophilic polymeric coating having a thickness of 20nm or less, the coating comprising hydrophilic polymers having pendentaryl ketone photoreactive groups, the hydrophilic polymers beingcovalently bonded via the reacted photo-reactive groups.